EP0366277B1 - Formulations pharmaceutiques - Google Patents
Formulations pharmaceutiques Download PDFInfo
- Publication number
- EP0366277B1 EP0366277B1 EP89309989A EP89309989A EP0366277B1 EP 0366277 B1 EP0366277 B1 EP 0366277B1 EP 89309989 A EP89309989 A EP 89309989A EP 89309989 A EP89309989 A EP 89309989A EP 0366277 B1 EP0366277 B1 EP 0366277B1
- Authority
- EP
- European Patent Office
- Prior art keywords
- formulation
- biologically active
- active material
- hydrophobic phase
- insulin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
- A61K38/215—IFN-beta
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/23—Calcitonins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/27—Growth hormone [GH] (Somatotropin)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/36—Blood coagulation or fibrinolysis factors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/49—Urokinase; Tissue plasminogen activator
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1275—Lipoproteins; Chylomicrons; Artificial HDL, LDL, VLDL, protein-free species thereof; Precursors thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
- A61K9/1676—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface having a drug-free core with discrete complete coating layer containing drug
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
- A61K9/5078—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings with drug-free core
Definitions
- hydrophilicity or hydrophobicity (lipophilicity) of the biologically active material is particularly critical
- the invention readily enables hydrophilic molecules such as insulin, calcitonin (especially salmon calcitonin) and growth hormones or somatotrophin (especially porcine somatotrophin), all of which (particularly salmon calcitonin) are so hydrophilic as to be hygroscopic.
- microemulsions as the term is used in this specification, is demonstrated by the fact that the microemulsions tend not to separate when left to stand; stability is "sufficient” if it allows for further processing, if desirable or necessary, and/or adequate shelf life. Furthermore, certain microemulsions can be translucent or transparent, often having a coloured tinge.
- absorbed lower-chained fatty acids are drained into the capillary blood and carried into the hepatic portal vein.
- Those lipids and fatty acids having relatively longer chains for example oleic acid and di-oleate and tri-oleate glycerides, as well as cholesterol and phospholipids, among other compounds which form chylomicrons within the membrane, are absorbed through the intestinal membrane wall by mechanisms which may not as yet be clearly understood. Once in the intestinal membrane, they participate in the formation of chylomicra and are then 'sucked' into the villae of the intestinal system, drained into the lymph fluid, collected the choracic duct and ultimately dumped into the systemic circulation.
- hydrophobic-phase miscible organic solvent may be present, again possibly as an aid in formulation.
- the nature of the solvent will depend on the other materials present. Ethanol is often suitable.
- the amount of solvent may be, for example from 5 to 50% v/v, based on the volume of the oil phase.
- each of the surfactants used in the preparation of formulations of this invention be selected from those surfactants classified as anionic or nonionic. These surfactants are particularly useful in pharmaceutical systems for their compatibility, stability, and non-toxicity.
- Surfactants generally suitable for the various purposes in the present invention include long chain (C16 to C24) fatty acids, e.g. palmitic acid, stearic acid and oleic acid; esters of long chain (C16 to C24) fatty acids, e.g. sodium palmitate, sodium stearate and sodium oleate; sodium lauryl sulphate; polyethylene glycol; polyethylene glycol alkyl ethers; fatty acid esters of polyethylene glycol, e.g.
- the surfactants of choice will of course be those which are currently on the approved list for pharmaceutical use and will have appropriately low LD50 values. There follows a list of certain exemplary surfactants, together with their HLB values and, where known, their LD50 values.
- Suitable high HLB surfactants are as follows:
- the liquid formulation can be coated onto the carrier in a variety of suitable ways, many of which will be well known in the art. Spray coating, for example in a fluidiser bed, is particularly suitable.
- the carrier will preferably be coated with from 50 to 500% of its weight with the liquid formulation.
- a solid orally administrable insulin-containing formulation is prepared as follows.
- Solid core carrier particles are prepared by mixing the following components: Ca carboxymethyl cellulose 200 g Alginic acid 75 g Gelatin 50 g Hydroxypropyl cellulose 175 g Sodium lauryl sulphate 25 g at 22°C.
- a test sample shows that the particles swell to 200 times their original volume when immersed in water at 38°C.
- the fluid bed coater/drier is shown, part-sectionally and part schematically in Figure 1, where it is represented generally by reference numeral 1.
- salmon calcitonin supplied by Rorer; also available from Sigma Chemical Co, St. Louis, Missouri, USA
- Sufficient salmon calcitonin is added to make 600 to 1200 IU per ml of the final formulation; 1000 IU per ml is the chosen amount.
- a solid orally administrable salmon calcitonin containing formulation was prepared broadly as described in Example 8, except that 500ml of the liquid formulation of Example 10 was coated onto 400g of carboxymethylcellulose, calcium salt in the modified SPIR-A-FLOW apparatus.
- Sub-mixture A is prepared from the following ingredients: Soya lecithin 150 g Glyceryl monooleate 22.46g Cholesterol 30 g Ethanol 50 ml by dissolving the first three ingredients in warm (75°C) ethanol and stirring until the other ingredients are dissolved. The ethanol is then evaporated off.
- a porcine somatotrophin-containing microemulsion is prepared from the following amounts of the sub-mixtures: Sub-mixture B 450 ml Sub-mixture C 150 ml Sub-mixture D 150 ml by adding sub-mixture C slowly to sub-mixture D while stirring with an AUTOHOMOMIXER homogeniser at 7500rpm at 20°C. The resultant mix is slowly added into sub-mixture B using the same mixer at the same temeprature and speed. The resulting emulsion is passed five consecutive times through a microfluidiser, as in Example 1, under the same conditions.
- Example 8 Using the general procedure of Example 7, but substituting an appropriate amount of human insulin, rather than bovine insulin, a corresponding orally ingestible human insulin formulation is prepared.
- the liquid formulation may be coated on a solid carrier as described in Example 8.
- tissue plasminogen activator rather than bovine insulin
- a corresponding orally ingestible tissue plasminogen activator formulation is prepared.
- the liquid formulation may be coated on a solid carrier as described in Example 8.
- Case numbers 1 and 8 are poor responders both to 500mg tablets, per os , of Diabensase and subcutaneously injected 20 units of Regular Insulin, as can be seen as follows:
Claims (61)
- Formulation pharmaceutique comprenant une microémulsion ayant une phase hydrophile et une phase hydrophobe, où(A) la phase hydrophile est dispersée dans la phase hydrophobe,(B) la phase hydrophile contient une matière biologiquement active, et(C) la phase hydrophobe contient des chylomicrons ou une matière à partir de laquelle les chylomicrons sont formés in vivo.
- Formulation suivant la revendication 1, où la phase hydrophile contient un solvant miscible à l'eau.
- Formulation suivant la revendication 1 ou 2, où la phase hydrophobe comprend des chylomicrons précipités de sérum humain, porcin ou bovin avec un polymère vinylique.
- Formulation suivant la revendication 1, 2 ou 3, où la phase hydrophobe comprend une matière qui forme les chylomicrons sur la muqueuse intestinale, une telle matière comprend une matière qui forme une matrice de chylomicrons, un phospholipide et un tensioactif lipophile.
- Formulation pharmaceutique comprenant une microémulsion ayant une phase hydrophile et une phase hydrophobe, où(A) la phase hydrophile est dispersée dans la phase hydrophobe,(B) la phase hydrophile contient une matière biologiquement active, et(C) la phase hydrophobe contient :(i) une matière qui forme une matrice de chylomicrons,(ii) un phospholipide, et(iii) un tensioactif lipophile.
- Formulation suivant la revendication 4 ou 5, où la matière qui forme la matrice de chylomicrons contient du cholestérol.
- Formulation suivant la revendication 4, 5 ou 6, où le phospholipide contient de la lécithine.
- Formulation suivant l'une quelconque des revendications 4 à 7, où le tensioactif lipophile comprend un acide gras à longue chaîne, estérifié sous forme d'ester de glycérol.
- Formulation suivant l'une quelconque des revendications 1 à 8, qui comprend un ester de cholestérol.
- Formulation suivant l'une quelconque des revendications 1 à 9, qui comprend une apoprotéine.
- Formulation suivant l'une quelconque des revendications 1 à 10, où la phase hydrophobe contient un solvant miscible dans la phase hydrophobe.
- Formulation suivant l'une quelconque des revendications 1 à 11, comprenant un tensioactif hydrophile ayant une valeur EHL d'au moins 17.
- Formulation suivant la revendication 12, où le tensioactif hydrophile comprend du monostéarate de PEG.
- Formulation suivant l'une quelconque des revendications 1 à 13, comprenant un tensioactif lipophile ayant une valeur EHL d'au moins 10.
- Formulation suivant la revendication 14, où le tensioactif lipophile comprend du monooléate de glycérol.
- Formulation suivant l'une quelconque des revendications 1 à 15, comprenant un ou plusieurs des :
inhibiteur de protéase;
stabilisateur de la matière biologiquement active;
aide à l'émulsion;
stabilisateur et/ou plastifiant, et/ou conservateur. - Formulation suivant la revendication 5, où la phase hydrophobe comprend :
% (v/v) Cholestérol (ou autre matrice) 0,5 - 5 Lécithine (ou autre phospholipide) 0,5 - 10 Tensioactif lipophile 0,5 - 95 Ester de cholestérol 0 - 5 Acide gras non estérifié 0 - 50 Apoprotéine 0 - 4 - Formulation suivant l'une quelconque des revendications 1 à 17, où la matière biologiquement active est protéinique.
- Formulation suivant la revendication 18, où la matière biologiquement active comprend l'insuline, l'interféron gamma ou l'interféron bêta.
- Formulation suivant la revendication 18, où la matière biologiquement active comprend l'insuline.
- Formulation suivant l'une quelconque des revendications 1 à 20, où la phase hydrophobe comprend :
% (v/v) Cholestérol (ou autre matrice) 0,5 - 5 Lécithine (ou autre phospholipide) 4 - 10 Tensioactif lipophile 50 - 95 Ester de cholestérol 0 - 5 Acide gras non estérifié 0 - 2 Apoprotéine 0 - 4 - Formulation suivant la revendication 18, où la matière biologiquement active comprend la calcitonine ou l'érythropoïétine.
- Formulation suivant la revendication 18, où la matière biologiquement active comprend la calcitonine de saumon.
- Formulation suivant l'une quelconque des revendications 1 à 20, 22 et 23, où la phase hydrophobe comprend :
% (v/v) Cholestérol (ou autre matrice) 0,5 - 5 Lécithine (ou autre phospholipide) 0,5 - 7 Tensioactif lipophile 0,5 - 5 Ester de cholestérol 0 - 5 Acide gras non estérifié 0 - 44 Apoprotéine 0 - 4 - Formulation suivant la revendication 18, où la matière biologiquement active est une hormone de croissance ou somatotrophine, un activateur de plasminogène tissulaire ou Facteur VIII.
- Formulation suivant la revendication 25, où la matière biologiquement active est de la somatotrophine porcine.
- Formulation suivant l'une quelconque des revendications 1 à 20, 22, 23, 25 ou 26, où la phase hydrophobe comprend :
% (v/v) Cholestérol (ou autre matrice) 0,5 - 5 Lécithine (ou autre phospholipide) 5 - 40 Tensioactif lipophile 10 - 70 Ester de cholestérol 0 - 5 Acide gras non estérifié 0 - 5 Apoprotéine 0 - 5 - Formulation suivant l'une quelconque des revendications 1 à 27, qui est sous forme solide et qui comprend un excipient solide enduit de la microémulsion.
- Formulation suivant la revendication 28, où l'excipient solide est une matière qui se dilate rapidement au contact d'un liquide aqueux.
- Formulation suivant la revendication 29, où l'excipient solide comprend :
% (p/p) Carboxyméthylcellulose calcique 20 - 60 Acide alginique 5 - 25 Gélatine 2 - 20 Hydroxypropylcellulose 20 - 60 Tensioactif 0,1 - 20 - Formulation suivant la revendication 28, où l'excipient solide a une valeur nutritionnelle.
- Formulation suivant la revendication 31, où l'excipient solide est protéinique.
- Formulation suivant la revendication 32, où l'excipient protéinique comprend de la poudre de soja.
- Formulation suivant l'une quelconque des revendications 1 à 33, qui est formulée pour être protégée de manière entérique.
- Formulation suivant la revendication 34, qui est solide et qui est protégée de manière entérique par du phtalate d'hydroxypropylméthylcellulose (HPMC-P).
- Formulation suivant l'une quelconque des revendications 1 à 35, qui est sous la forme d'une capsule.
- Formulation suivant la revendication 36, où la coque de la capsule contient de la gélatine dure.
- Formulation suivant la revendication 37, où la coque de gélatine dure est protégée de manière entérique par du HPMC-P.
- Utilisation d'ingrédients d'une formulation suivant l'une quelconque des revendications 1 à 38, dans la préparation d'une formulation administrable par voie orale ou rectale pour le traitement ou la prophylaxie d'un désordre susceptible d'être traité ou contrôlé par une matière biologiquement active.
- Utilisation suivant la revendication 39, où la matière biologiquement active est de l'insuline et le désordre est le diabète.
- Utilisation suivant la revendication 39, où la matière biologiquement active est de la calcitonine et le désordre est susceptible d'être géré par de la calcitonine.
- Utilisation suivant la revendication 39, où la matière biologiquement active est une hormone de croissance et le désordre est susceptible d'être géré par une hormone de croissance.
- Procédé d'élevage d'un animal, le procédé comprenant l'administration à l'animal d'une quantité efficace d'une formulation suivant l'une quelconque des revendications 1 à 38, où la formulation est non thérapeutique.
- Procédé pour la préparation d'une formulation suivant l'une quelconque des revendications 1 à 38, susceptible d'être ingérée par voie orale ou rectale, le procédé comprenant le mélange des ingrédients.
- Procédé suivant la revendication 44, comprenant l'addition d'au moins quelques-uns des composants de la phase hydrophile à au moins quelques-uns des composants de la phase hydrophobe, sous mélange rapide et l'addition des composants restants.
- Procédé suivant la revendication 44 ou 45, comprenant :(a) un mélange rapide de la matière biologiquement active dans un solvant hydrophile approprié avec la phase hydrophobe, qui contient un tensioactif lipophile, et(b) facultativement, l'addition d'un tensioactif hydrophile avec un mélange rapide supplémentaire.
- Procédé suivant la revendication 44, 45 ou 46, comprenant l'exposition du mélange résultant à l'action d'un appareil de microfluidisation.
- Procédé suivant la revendication 47, ou le mélange est passé trois fois dans un appareil de microfluidisation.
- Procédé suivant l'une quelconque des revendications 44 à 48, comprenant le revêtement d'un excipient solide avec la formulation ainsi formée.
- Procédé suivant la revendication 49, où l'excipient solide est enduit par vaporisation.
- Procédé suivant la revendication 50, où le revêtement par vaporisation est réalisé dans un lit de fluidisation.
- Procédé suivant la revendication 51, où le gaz de fluidisation est chauffé quand la température dans le lit de fluidisation est trop faible et où le gaz de fluidisation est refroidi quand la température dans le lit de fluidisation est trop élevée.
- Procédé suivant la revendication 51 ou 52, où le revêtement par vaporisation est réalisé à une température de 29°C ± 5°C.
- Procédé suivant l'une quelconque des revendications 50 à 53, où le revêtement par vaporisation est intermittent.
- Procédé suivant l'une quelconque des revendications 49 à 54, où les particules enduites d'excipient sont granulées.
- Procédé suivant l'une quelconque des revendications 49 à 55, où les particules enduites d'excipient sont revêtues de manière entérique.
- Procédé suivant l'une quelconque des revendications 44 à 56, où la formulation est encapsulée dans une capsule.
- Procédé suivant la revendication 57, où la coque de la capsule contient de la gélatine dure.
- Procédé suivant la revendication 58, où la coque de gélatine dure est protégée de manière entérique par du HPMC-P.
- Procédé suivant la revendication 59, le procédé comprenant d'abord le revêtement de la capsule avec une matière capable de protéger la gélatine de la capsule des effets nuisibles du chlorure de méthylène et, ensuite, le revêtement de la capsule ainsi protégée par du phtalate d'hydroxypropylméthylcellulose (HPMC-P) au moyen d'une solution de HPMC-P dans du chlorure de méthylène.
- Procédé suivant la revendication 60, où la première couche protectrice comprend un mélange de PVP et de HPMC.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AT89309989T ATE98480T1 (de) | 1988-09-29 | 1989-09-29 | Arzneimittelformulierungen. |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB8822857 | 1988-09-29 | ||
GB888822857A GB8822857D0 (en) | 1988-09-29 | 1988-09-29 | Pharmaceutical formulations |
Publications (3)
Publication Number | Publication Date |
---|---|
EP0366277A2 EP0366277A2 (fr) | 1990-05-02 |
EP0366277A3 EP0366277A3 (en) | 1990-11-28 |
EP0366277B1 true EP0366277B1 (fr) | 1993-12-15 |
Family
ID=10644447
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP89309989A Expired - Lifetime EP0366277B1 (fr) | 1988-09-29 | 1989-09-29 | Formulations pharmaceutiques |
Country Status (28)
Country | Link |
---|---|
US (1) | US5656289A (fr) |
EP (1) | EP0366277B1 (fr) |
JP (1) | JP2927835B2 (fr) |
KR (1) | KR0139641B1 (fr) |
AR (1) | AR243375A1 (fr) |
AT (1) | ATE98480T1 (fr) |
AU (2) | AU625498B2 (fr) |
BG (1) | BG60849B1 (fr) |
CA (1) | CA1339814C (fr) |
CZ (1) | CZ285237B6 (fr) |
DD (1) | DD300405A5 (fr) |
DE (1) | DE68911473T2 (fr) |
DK (1) | DK481989A (fr) |
ES (1) | ES2060785T3 (fr) |
FI (1) | FI98196C (fr) |
GB (1) | GB8822857D0 (fr) |
HK (1) | HK85596A (fr) |
HU (2) | HUT54033A (fr) |
IE (1) | IE63543B1 (fr) |
MX (1) | MX17752A (fr) |
NO (1) | NO300199B1 (fr) |
NZ (1) | NZ230838A (fr) |
PL (1) | PL163635B1 (fr) |
PT (1) | PT91850B (fr) |
RO (1) | RO108219B1 (fr) |
RU (1) | RU2122403C1 (fr) |
WO (1) | WO1990003164A2 (fr) |
ZA (1) | ZA897437B (fr) |
Cited By (40)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5541155A (en) | 1994-04-22 | 1996-07-30 | Emisphere Technologies, Inc. | Acids and acid salts and their use in delivery systems |
US5578323A (en) | 1992-06-15 | 1996-11-26 | Emisphere Technologies, Inc. | Proteinoid carriers and methods for preparation and use thereof |
US5601846A (en) | 1992-06-15 | 1997-02-11 | Emisphere Technologies, Inc. | Proteinoid microspheres and methods for preparation and use thereof |
US5629020A (en) | 1994-04-22 | 1997-05-13 | Emisphere Technologies, Inc. | Modified amino acids for drug delivery |
US5643957A (en) | 1993-04-22 | 1997-07-01 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5650386A (en) | 1995-03-31 | 1997-07-22 | Emisphere Technologies, Inc. | Compositions for oral delivery of active agents |
US5667806A (en) | 1995-06-07 | 1997-09-16 | Emisphere Technologies, Inc. | Spray drying method and apparatus |
US5693338A (en) | 1994-09-29 | 1997-12-02 | Emisphere Technologies, Inc. | Diketopiperazine-based delivery systems |
US5709861A (en) | 1993-04-22 | 1998-01-20 | Emisphere Technologies, Inc. | Compositions for the delivery of antigens |
US5714167A (en) | 1992-06-15 | 1998-02-03 | Emisphere Technologies, Inc. | Active agent transport systems |
US5750147A (en) | 1995-06-07 | 1998-05-12 | Emisphere Technologies, Inc. | Method of solubilizing and encapsulating itraconazole |
US5766633A (en) | 1993-04-22 | 1998-06-16 | Emisphere Technologies, Inc. | Oral drug delivery compositions and methods |
US5792451A (en) | 1994-03-02 | 1998-08-11 | Emisphere Technologies, Inc. | Oral drug delivery compositions and methods |
US5804688A (en) | 1997-02-07 | 1998-09-08 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5811127A (en) | 1992-06-15 | 1998-09-22 | Emisphere Technologies, Inc. | Desferrioxamine oral delivery system |
US5820881A (en) | 1995-04-28 | 1998-10-13 | Emisphere Technologies, Inc. | Microspheres of diamide-dicarboxylic acids |
US5824345A (en) | 1995-06-07 | 1998-10-20 | Emisphere Technologies, Inc. | Fragrances and flavorants |
US5863944A (en) | 1997-04-30 | 1999-01-26 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5866536A (en) | 1995-03-31 | 1999-02-02 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5876710A (en) | 1997-02-07 | 1999-03-02 | Emisphere Technologies Inc. | Compounds and compositions for delivering active agents |
US5879681A (en) | 1997-02-07 | 1999-03-09 | Emisphere Technolgies Inc. | Compounds and compositions for delivering active agents |
US5939381A (en) | 1997-02-07 | 1999-08-17 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5958457A (en) | 1993-04-22 | 1999-09-28 | Emisphere Technologies, Inc. | Compositions for the delivery of antigens |
US5962710A (en) | 1997-05-09 | 1999-10-05 | Emisphere Technologies, Inc. | Method of preparing salicyloylamino acids |
US5965121A (en) | 1995-03-31 | 1999-10-12 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5972387A (en) | 1992-12-21 | 1999-10-26 | Emisphere Technologies, Inc. | Modified hydrolyzed vegetable protein microspheres and methods for preparation and use thereof |
US5990166A (en) | 1997-02-07 | 1999-11-23 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5989539A (en) | 1995-03-31 | 1999-11-23 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US6001347A (en) | 1995-03-31 | 1999-12-14 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US6051258A (en) | 1995-06-07 | 2000-04-18 | Emisphere Technologies, Inc. | Proteinoid emulsions and methods for preparation and use thereof |
US6060513A (en) | 1997-02-07 | 2000-05-09 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US6071510A (en) | 1995-03-31 | 2000-06-06 | Emisphere Technologies, Inc. | Modified amino acids and compositions comprising the same for delivering active agents |
US6084112A (en) | 1995-09-11 | 2000-07-04 | Emisphere Technologies, Inc. | Method for preparing ω-aminoalkanoic acid derivatives from cycloalkanones |
US6090958A (en) | 1995-03-31 | 2000-07-18 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US6099856A (en) | 1992-06-15 | 2000-08-08 | Emisphere Technologies, Inc. | Active agent transport systems |
US6221367B1 (en) | 1992-06-15 | 2001-04-24 | Emisphere Technologies, Inc. | Active agent transport systems |
US6242495B1 (en) | 1997-02-07 | 2001-06-05 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US6331318B1 (en) | 1994-09-30 | 2001-12-18 | Emisphere Technologies Inc. | Carbon-substituted diketopiperazine delivery systems |
US6375983B1 (en) | 1996-06-14 | 2002-04-23 | Emisphere Technologies, Inc. | Microencapsulated fragrances and method for preparation |
US8241670B2 (en) | 2004-04-15 | 2012-08-14 | Chiasma Inc. | Compositions capable of facilitating penetration across a biological barrier |
Families Citing this family (94)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5447728A (en) * | 1992-06-15 | 1995-09-05 | Emisphere Technologies, Inc. | Desferrioxamine oral delivery system |
US5451410A (en) * | 1993-04-22 | 1995-09-19 | Emisphere Technologies, Inc. | Modified amino acids for encapsulating active agents |
GB9022788D0 (en) * | 1990-10-19 | 1990-12-05 | Cortecs Ltd | Pharmaceutical formulations |
US5206219A (en) * | 1991-11-25 | 1993-04-27 | Applied Analytical Industries, Inc. | Oral compositions of proteinaceous medicaments |
DE4140185C2 (de) * | 1991-12-05 | 1996-02-01 | Alfatec Pharma Gmbh | Ein 2-Arylpropionsäurederivat in Nanosolform enthaltendes Arzneimittel und seine Herstellung |
DE4140179C2 (de) * | 1991-12-05 | 1995-12-21 | Alfatec Pharma Gmbh | Akutform für ein Ibuprofen enthaltendes Arzneimittel |
US5614219A (en) * | 1991-12-05 | 1997-03-25 | Alfatec-Pharma Gmbh | Oral administration form for peptide pharmaceutical substances, in particular insulin |
JPH06510796A (ja) * | 1991-12-18 | 1994-12-01 | ファイザー インク. | 酵素による不活性化から生物活性ペプチドを保護するための医薬組成物におけるダイズタンパク質又は加水分解物 |
US5525519A (en) * | 1992-01-07 | 1996-06-11 | Middlesex Sciences, Inc. | Method for isolating biomolecules from a biological sample with linear polymers |
BR9201168A (pt) * | 1992-04-02 | 1994-04-12 | Zerbini E J Fundacao | Microemulsoes usadas como velculo para carregar quimioterapicos as celulas neoplasicas |
US6153592A (en) * | 1992-11-09 | 2000-11-28 | Port Systems, Llc | Enhancing the bioavailability of proteolytically labile therapeutic agents |
AU686149B2 (en) * | 1993-04-19 | 1998-02-05 | Institute For Advanced Skin Research Inc. | Microemulsion preparation containing difficultly absorbable substance |
US5514670A (en) * | 1993-08-13 | 1996-05-07 | Pharmos Corporation | Submicron emulsions for delivery of peptides |
US5744155A (en) * | 1993-08-13 | 1998-04-28 | Friedman; Doron | Bioadhesive emulsion preparations for enhanced drug delivery |
DE69418717D1 (de) * | 1993-09-29 | 1999-07-01 | Technobiochip | Duenne proteinschichten und zusammensetzungen zu ihrer herstellung |
ATE198547T1 (de) * | 1993-11-03 | 2001-01-15 | Isomed Inc | Mizelleförmige feinteilige pharmazeutische zusammensetzungen |
GB9325445D0 (en) * | 1993-12-13 | 1994-02-16 | Cortecs Ltd | Pharmaceutical formulations |
US5858398A (en) * | 1994-11-03 | 1999-01-12 | Isomed Inc. | Microparticular pharmaceutical compositions |
GB9424902D0 (en) * | 1994-12-09 | 1995-02-08 | Cortecs Ltd | Solubilisation Aids |
AU4862796A (en) * | 1995-02-06 | 1996-08-27 | Nanosystems L.L.C. | Formulations of compounds as nanoparticulate dispersions in digestible oils or fatty acids |
AUPN801296A0 (en) * | 1996-02-12 | 1996-03-07 | Csl Limited | Stabilised growth hormone formulation and method of preparation thereof |
AU716747B2 (en) * | 1996-02-12 | 2000-03-02 | Csl Limited | Stabilised growth hormone formulation and method of preparation thereof |
EP0910343A1 (fr) * | 1996-07-03 | 1999-04-28 | University Of Pittsburgh | Formulations d'emulsions pour des agents actifs hydrophiles |
US6465016B2 (en) * | 1996-08-22 | 2002-10-15 | Research Triangle Pharmaceuticals | Cyclosporiine particles |
US7255877B2 (en) * | 1996-08-22 | 2007-08-14 | Jagotec Ag | Fenofibrate microparticles |
US6150164A (en) * | 1996-09-30 | 2000-11-21 | The Regents Of The University Of Michigan | Methods and compositions of a bioartificial kidney suitable for use in vivo or ex vivo |
ES2130056B1 (es) * | 1997-01-16 | 2000-02-01 | Lipotec Sa | Un nuevo preparado farmaceutico para mejorar la biodisponibilidad oral de drogas de dificil absorcion. |
US6054421A (en) * | 1997-09-23 | 2000-04-25 | Scimed Life Systems, Inc. | Medical emulsion lubricant |
US6281175B1 (en) | 1997-09-23 | 2001-08-28 | Scimed Life Systems, Inc. | Medical emulsion for lubrication and delivery of drugs |
US6221378B1 (en) | 1998-02-10 | 2001-04-24 | Generex Pharmaceuticals Incorporated | Mixed micellar delivery system and method of preparation |
US6017545A (en) * | 1998-02-10 | 2000-01-25 | Modi; Pankaj | Mixed micellar delivery system and method of preparation |
US7070799B1 (en) * | 1998-02-10 | 2006-07-04 | Generex Pharmaceuticals, Inc. | Method for administering insulin to the buccal region |
DK1079808T3 (da) | 1998-05-29 | 2004-06-07 | Skyepharma Canada Inc | Præparater med termisk beskyttede mikropartikler og fremgangsmåde til slutdampsterilisering deraf |
US6660277B1 (en) | 1998-06-19 | 2003-12-09 | Avon Products, Inc. | Gel matrix non-emulsion composition containing two clay gels |
CA2339991C (fr) * | 1998-08-13 | 2007-01-02 | Cima Labs Inc. | Microemulsions comme formes pharmaceutiques solides destinees a une administration orale |
IL143197A0 (en) | 1998-11-20 | 2002-04-21 | Rtp Pharma Inc | Dispersible phospholipid stabilized microparticles |
DE19855819C2 (de) * | 1998-12-03 | 2001-02-15 | Roche Diagnostics Gmbh | Stabilisierung von Cytokeratin enthaltenden Kalibratoren |
AU769539B2 (en) | 1999-01-29 | 2004-01-29 | Zoetis Services Llc | Adjuvants for use in vaccines |
US6267985B1 (en) | 1999-06-30 | 2001-07-31 | Lipocine Inc. | Clear oil-containing pharmaceutical compositions |
US6761903B2 (en) | 1999-06-30 | 2004-07-13 | Lipocine, Inc. | Clear oil-containing pharmaceutical compositions containing a therapeutic agent |
US6294192B1 (en) * | 1999-02-26 | 2001-09-25 | Lipocine, Inc. | Triglyceride-free compositions and methods for improved delivery of hydrophobic therapeutic agents |
US6248354B1 (en) * | 1999-03-04 | 2001-06-19 | Allergan Sales, Inc. | Capsule system |
CN1165339C (zh) | 1999-04-09 | 2004-09-08 | 奥索-麦克尼尔药品公司 | 红细胞生成素药物组合物 |
US6176849B1 (en) * | 1999-05-21 | 2001-01-23 | Scimed Life Systems, Inc. | Hydrophilic lubricity coating for medical devices comprising a hydrophobic top coat |
US6610035B2 (en) | 1999-05-21 | 2003-08-26 | Scimed Life Systems, Inc. | Hydrophilic lubricity coating for medical devices comprising a hybrid top coat |
US6309663B1 (en) | 1999-08-17 | 2001-10-30 | Lipocine Inc. | Triglyceride-free compositions and methods for enhanced absorption of hydrophilic therapeutic agents |
US6982281B1 (en) * | 2000-11-17 | 2006-01-03 | Lipocine Inc | Pharmaceutical compositions and dosage forms for administration of hydrophobic drugs |
US6458383B2 (en) | 1999-08-17 | 2002-10-01 | Lipocine, Inc. | Pharmaceutical dosage form for oral administration of hydrophilic drugs, particularly low molecular weight heparin |
AU730929B2 (en) * | 1999-07-06 | 2001-03-22 | Nestec S.A. | Composition and method for prolonging the useful life of enteral feeding tubes |
US7732404B2 (en) | 1999-12-30 | 2010-06-08 | Dexcel Ltd | Pro-nanodispersion for the delivery of cyclosporin |
US6417237B1 (en) * | 2000-06-08 | 2002-07-09 | The Board Of Trustees Of The University Of Illinois | Macromolecular drug complexes and compositions containing the same |
US6692771B2 (en) * | 2001-02-23 | 2004-02-17 | Cima Labs Inc. | Emulsions as solid dosage forms for oral administration |
US6951655B2 (en) * | 2001-10-11 | 2005-10-04 | Imi Biomed, Inc. | Pro-micelle pharmaceutical compositions |
DE10158447B4 (de) * | 2001-11-30 | 2005-02-10 | Aquanova German Solubilisate Technologies (Agt) Gmbh | Ascorbinsäure-Solubilisat |
ITMI20012694A1 (it) * | 2001-12-19 | 2003-06-19 | Remedia S R L | Composizione farmaceutica comprendente una microemulsione doppia olio/acqua/olio incorporata in un supporto solido |
SI21258A (sl) * | 2002-07-17 | 2004-02-29 | LEK farmacevtska dru�ba d.d. | Stabilni farmacevtski pripravek, ki vsebuje eritropoietin in poloksamerni poliol |
KR100533460B1 (ko) * | 2002-07-20 | 2005-12-08 | 대화제약 주식회사 | 난용성 약물의 가용화용 점막흡착성 조성물, 이를 이용한난용성 약물의 가용화용 제형 및 이들의 제조 방법 |
EP1537880A4 (fr) * | 2002-09-11 | 2009-07-01 | Takeda Pharmaceutical | Preparation a liberation prolongee |
FR2851918B1 (fr) * | 2003-03-06 | 2006-06-16 | Poudre impregnee ameliorant la biodisponibilite et/ou la solubilite et procede de fabrication | |
EP1537876A1 (fr) * | 2003-12-01 | 2005-06-08 | BioGeneriX AG | Formulation d'une solution d'érythropoiétine |
US20080254115A1 (en) * | 2004-05-19 | 2008-10-16 | Rubino Orapin P | Micropellet Containing Pellets and Method of Preparing Such Pellets |
EP1652513A1 (fr) * | 2004-11-02 | 2006-05-03 | Denderah Pharm Sa | Micelles inversées basés sur des stérols et des acylglycerols and leur utilisation thérapeutique |
US20070071779A1 (en) * | 2005-09-26 | 2007-03-29 | Leggit Ingenuity, Llc | Compositions for delivering lipophilic agents to the intestinal mucosa and method of making thereof |
WO2007127787A2 (fr) * | 2006-04-25 | 2007-11-08 | Joslin Diabetes Center, Inc. | Lymphocytes t cd4+ de régulation spécifique auto-antigénique de l'insuline |
US9918934B2 (en) * | 2006-12-12 | 2018-03-20 | Edgar Joel Acosta-Zara | Linker-based lecithin microemulsion delivery vehicles |
EP1985188B1 (fr) * | 2007-04-24 | 2013-02-27 | Generale Biscuit | Procédé pour la pulvérisation d'une couche contenant des graisses et du sucre dans un produit comestible |
WO2009042114A2 (fr) | 2007-09-21 | 2009-04-02 | The Johns Hopkins University | Dérivés de phénazine et leurs utilisations |
JP5156458B2 (ja) * | 2008-03-31 | 2013-03-06 | 理研ビタミン株式会社 | ソフトカプセル充填用液状組成物 |
KR101503474B1 (ko) * | 2007-09-27 | 2015-03-18 | 리켄 비타민 가부시키가이샤 | 연질 캅셀 충전용 액상 조성물 |
HUE033611T2 (en) * | 2008-09-17 | 2017-12-28 | Chiasma Inc | Pharmaceutical preparations and associated dosing procedures |
US11304960B2 (en) | 2009-01-08 | 2022-04-19 | Chandrashekar Giliyar | Steroidal compositions |
US9309378B2 (en) | 2009-06-19 | 2016-04-12 | Exacto, Inc. | Emulsion compositions comprising polyacrylamide copolymer and ethylene oxide—propylene oxide copolymer |
US9307758B2 (en) | 2009-06-19 | 2016-04-12 | Exacto, Inc. | Polyacrylamide based agricultural compositions |
US9428630B2 (en) | 2009-06-19 | 2016-08-30 | Exacto, Inc. | Water-in-oil polyacrylamide-based microemulsions and related methods |
CN101756900B (zh) * | 2010-02-25 | 2012-05-30 | 谢恬 | 一种榄香烯微乳 |
JP5406110B2 (ja) * | 2010-04-20 | 2014-02-05 | 日東電工株式会社 | 半導体ウエハ加工用粘着シート |
US9358241B2 (en) | 2010-11-30 | 2016-06-07 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
US20180153904A1 (en) | 2010-11-30 | 2018-06-07 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
US9034858B2 (en) | 2010-11-30 | 2015-05-19 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
US20120148675A1 (en) | 2010-12-10 | 2012-06-14 | Basawaraj Chickmath | Testosterone undecanoate compositions |
EP3079721B1 (fr) * | 2013-12-11 | 2024-04-10 | Health-Ever Biotech Co. Ltd. | Compositions pharmaceutiques à base de caroténoïde |
WO2016033549A2 (fr) | 2014-08-28 | 2016-03-03 | Lipocine Inc. | Compositions de (17-ss)-3-oxoandrost-4-èn-17-yl tridécanoate et leurs procédés de préparation et d'utilisation |
US9498485B2 (en) | 2014-08-28 | 2016-11-22 | Lipocine Inc. | Bioavailable solid state (17-β)-hydroxy-4-androsten-3-one esters |
WO2016126830A1 (fr) | 2015-02-03 | 2016-08-11 | Chiasma Inc. | Méthode de traitement de maladies |
US10328087B2 (en) | 2015-07-23 | 2019-06-25 | Therapeuticsmd, Inc. | Formulations for solubilizing hormones |
US10286077B2 (en) | 2016-04-01 | 2019-05-14 | Therapeuticsmd, Inc. | Steroid hormone compositions in medium chain oils |
JP2019513709A (ja) | 2016-04-01 | 2019-05-30 | セラピューティックスエムディー インコーポレーテッドTherapeuticsmd, Inc. | ステロイドホルモン薬学的組成物 |
US11559530B2 (en) | 2016-11-28 | 2023-01-24 | Lipocine Inc. | Oral testosterone undecanoate therapy |
GB201808564D0 (en) | 2018-05-24 | 2018-07-11 | Douglas Pharmaceuticals Ltd | Treatments |
EP3820455A1 (fr) * | 2018-07-10 | 2021-05-19 | Universidade de Santiago de Compostela | Système lipidique nanostructuré |
DE102019211195A1 (de) * | 2019-07-26 | 2021-01-28 | Add Advanced Drug Delivery Technologies Ltd. | Verfahren und Vorrichtung zur Herstellung eines im Wesentlichen im wässrigen Milieu lösbaren Cannabinoid-Granulats |
US11141457B1 (en) | 2020-12-28 | 2021-10-12 | Amryt Endo, Inc. | Oral octreotide therapy and contraceptive methods |
JP2024507002A (ja) * | 2021-02-08 | 2024-02-15 | カプスゲル・ベルジャン・エヌ ブイ | 延長放出ビタミンc及びその製造 |
WO2023017537A1 (fr) | 2021-08-12 | 2023-02-16 | Celagenex Research (India) Pvt. Ltd. | Composition peptidique orale perméable au tractus gastro-intestinal à base d'huile algale |
Family Cites Families (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4165385A (en) * | 1973-05-29 | 1979-08-21 | Dianis Creations, Inc. | Water-in-oil emulsion for skin moisturizing |
US4146499A (en) * | 1976-09-18 | 1979-03-27 | Rosano Henri L | Method for preparing microemulsions |
JPS5517328A (en) * | 1978-07-21 | 1980-02-06 | Tanabe Seiyaku Co Ltd | Insulin-containing emulsion and its preparation |
JPS55153713A (en) * | 1979-05-02 | 1980-11-29 | Kureha Chem Ind Co Ltd | Pharmaceutical preparation of ribosome containing active substance |
JPS5770814A (en) * | 1980-10-17 | 1982-05-01 | Isamu Horikoshi | Oral preparation of blood clotting eighth factor |
JPS5772920A (en) * | 1980-10-27 | 1982-05-07 | Toyama Chem Co Ltd | Carcinostatic agent containing blood plasma or blood serumal lipoprotein |
JPS5821622A (ja) * | 1981-07-28 | 1983-02-08 | Kowa Co | 糖尿病治療用薬剤 |
JPS5916534A (ja) * | 1982-07-19 | 1984-01-27 | Lion Corp | 非イオン性界面活性剤系ベシクル分散液 |
JPS6058915A (ja) * | 1983-09-12 | 1985-04-05 | Fujisawa Pharmaceut Co Ltd | 薬物含有脂質小胞体製剤 |
JPS60155109A (ja) * | 1984-01-23 | 1985-08-15 | Terumo Corp | リポソ−ム製剤 |
JPS6172721A (ja) * | 1984-09-19 | 1986-04-14 | Daigo Eiyou Kagaku Kk | インシユリン含有リポゾ−ム |
FR2581543B1 (fr) * | 1985-05-09 | 1989-07-07 | Tressens Dominique | Pharmacotechnie permettant la realisation d'une preparation insulinique active par voie orale |
US4849227A (en) * | 1986-03-21 | 1989-07-18 | Eurasiam Laboratories, Inc. | Pharmaceutical compositions |
US4851220A (en) * | 1986-11-26 | 1989-07-25 | Schering Corporation | Stable oleaginous gel |
NZ222907A (en) * | 1986-12-16 | 1990-08-28 | Novo Industri As | Preparation for intranasal administration containing a phospholipid absorption enhancing system |
US4839111A (en) * | 1987-02-02 | 1989-06-13 | The University Of Tennessee Research Corporation | Preparation of solid core liposomes |
US4855090A (en) * | 1987-03-13 | 1989-08-08 | Micro-Pak, Inc. | Method of producing high aqueous volume multilamellar vesicles |
US4853228A (en) * | 1987-07-28 | 1989-08-01 | Micro-Pak, Inc. | Method of manufacturing unilamellar lipid vesicles |
JPH06172721A (ja) * | 1992-09-03 | 1994-06-21 | Hitachi Kasei Polymer Kk | 研磨材固定用テープ |
-
1988
- 1988-09-29 GB GB888822857A patent/GB8822857D0/en active Pending
-
1989
- 1989-09-28 HU HU895107A patent/HUT54033A/hu unknown
- 1989-09-29 ZA ZA897437A patent/ZA897437B/xx unknown
- 1989-09-29 NO NO893896A patent/NO300199B1/no not_active IP Right Cessation
- 1989-09-29 CZ CS895548A patent/CZ285237B6/cs not_active IP Right Cessation
- 1989-09-29 AU AU42432/89A patent/AU625498B2/en not_active Ceased
- 1989-09-29 DD DD333127A patent/DD300405A5/de unknown
- 1989-09-29 NZ NZ230838A patent/NZ230838A/en unknown
- 1989-09-29 AT AT89309989T patent/ATE98480T1/de active
- 1989-09-29 DK DK481989A patent/DK481989A/da not_active Application Discontinuation
- 1989-09-29 AR AR89315058A patent/AR243375A1/es active
- 1989-09-29 CA CA000614764A patent/CA1339814C/fr not_active Expired - Fee Related
- 1989-09-29 BG BG89877A patent/BG60849B1/bg unknown
- 1989-09-29 DE DE89309989T patent/DE68911473T2/de not_active Expired - Lifetime
- 1989-09-29 RU SU4742283A patent/RU2122403C1/ru active
- 1989-09-29 EP EP89309989A patent/EP0366277B1/fr not_active Expired - Lifetime
- 1989-09-29 RO RO141815A patent/RO108219B1/ro unknown
- 1989-09-29 FI FI894637A patent/FI98196C/fi not_active IP Right Cessation
- 1989-09-29 PT PT91850A patent/PT91850B/pt not_active IP Right Cessation
- 1989-09-29 ES ES89309989T patent/ES2060785T3/es not_active Expired - Lifetime
- 1989-09-29 JP JP1255067A patent/JP2927835B2/ja not_active Expired - Lifetime
- 1989-09-29 IE IE311889A patent/IE63543B1/en not_active IP Right Cessation
- 1989-09-29 KR KR1019890014062A patent/KR0139641B1/ko not_active IP Right Cessation
- 1989-09-29 AU AU43417/89A patent/AU4341789A/en not_active Abandoned
- 1989-09-29 WO PCT/GB1989/001161 patent/WO1990003164A2/fr unknown
- 1989-09-29 PL PL89281635A patent/PL163635B1/pl unknown
- 1989-10-29 MX MX1775289A patent/MX17752A/es unknown
-
1994
- 1994-02-16 US US08/207,236 patent/US5656289A/en not_active Expired - Fee Related
-
1995
- 1995-06-29 HU HU95P/P00585P patent/HU211633A9/hu unknown
-
1996
- 1996-05-16 HK HK85596A patent/HK85596A/xx not_active IP Right Cessation
Non-Patent Citations (1)
Title |
---|
PATENT ABSTRACTS OF JAPAN, vol. 7, no. 97, (C-163)(1242), 23 April 1983# * |
Cited By (54)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6071538A (en) | 1992-06-15 | 2000-06-06 | Emisphere Technologies, Inc. | Oral delivery composition comprising supramolecular complex |
US5578323A (en) | 1992-06-15 | 1996-11-26 | Emisphere Technologies, Inc. | Proteinoid carriers and methods for preparation and use thereof |
US5601846A (en) | 1992-06-15 | 1997-02-11 | Emisphere Technologies, Inc. | Proteinoid microspheres and methods for preparation and use thereof |
US6413550B1 (en) | 1992-06-15 | 2002-07-02 | Emisphere Technologies, Inc. | Proteinoid carriers and methods for preparation and use thereof |
US5840340A (en) | 1992-06-15 | 1998-11-24 | Emisphere Technologies, Inc. | Proteinoid carriers and methods for preparation and use thereof |
US6348207B1 (en) | 1992-06-15 | 2002-02-19 | Emisiphere Technologies, Inc. | Orally deliverable supramolecular complex |
US6245359B1 (en) | 1992-06-15 | 2001-06-12 | Emisphere Technologies, Inc. | Active agent transport systems |
US6221367B1 (en) | 1992-06-15 | 2001-04-24 | Emisphere Technologies, Inc. | Active agent transport systems |
US5714167A (en) | 1992-06-15 | 1998-02-03 | Emisphere Technologies, Inc. | Active agent transport systems |
US6099856A (en) | 1992-06-15 | 2000-08-08 | Emisphere Technologies, Inc. | Active agent transport systems |
US5811127A (en) | 1992-06-15 | 1998-09-22 | Emisphere Technologies, Inc. | Desferrioxamine oral delivery system |
US5972387A (en) | 1992-12-21 | 1999-10-26 | Emisphere Technologies, Inc. | Modified hydrolyzed vegetable protein microspheres and methods for preparation and use thereof |
US5709861A (en) | 1993-04-22 | 1998-01-20 | Emisphere Technologies, Inc. | Compositions for the delivery of antigens |
US6100298A (en) | 1993-04-22 | 2000-08-08 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5766633A (en) | 1993-04-22 | 1998-06-16 | Emisphere Technologies, Inc. | Oral drug delivery compositions and methods |
US5955503A (en) | 1993-04-22 | 1999-09-21 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5958457A (en) | 1993-04-22 | 1999-09-28 | Emisphere Technologies, Inc. | Compositions for the delivery of antigens |
US5643957A (en) | 1993-04-22 | 1997-07-01 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5792451A (en) | 1994-03-02 | 1998-08-11 | Emisphere Technologies, Inc. | Oral drug delivery compositions and methods |
US6180140B1 (en) | 1994-04-22 | 2001-01-30 | Emisphere Technologies, Inc. | Modified amino acids for drug delivery |
US5629020A (en) | 1994-04-22 | 1997-05-13 | Emisphere Technologies, Inc. | Modified amino acids for drug delivery |
US5541155A (en) | 1994-04-22 | 1996-07-30 | Emisphere Technologies, Inc. | Acids and acid salts and their use in delivery systems |
US5976569A (en) | 1994-09-29 | 1999-11-02 | Emisphere Technologies, Inc. | Diketopiperazine-based delivery systems |
US5693338A (en) | 1994-09-29 | 1997-12-02 | Emisphere Technologies, Inc. | Diketopiperazine-based delivery systems |
US6331318B1 (en) | 1994-09-30 | 2001-12-18 | Emisphere Technologies Inc. | Carbon-substituted diketopiperazine delivery systems |
US6001347A (en) | 1995-03-31 | 1999-12-14 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US6071510A (en) | 1995-03-31 | 2000-06-06 | Emisphere Technologies, Inc. | Modified amino acids and compositions comprising the same for delivering active agents |
US6428780B2 (en) | 1995-03-31 | 2002-08-06 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5650386A (en) | 1995-03-31 | 1997-07-22 | Emisphere Technologies, Inc. | Compositions for oral delivery of active agents |
US6346242B1 (en) | 1995-03-31 | 2002-02-12 | Emishpere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5989539A (en) | 1995-03-31 | 1999-11-23 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US6090958A (en) | 1995-03-31 | 2000-07-18 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5866536A (en) | 1995-03-31 | 1999-02-02 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5965121A (en) | 1995-03-31 | 1999-10-12 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5820881A (en) | 1995-04-28 | 1998-10-13 | Emisphere Technologies, Inc. | Microspheres of diamide-dicarboxylic acids |
US5824345A (en) | 1995-06-07 | 1998-10-20 | Emisphere Technologies, Inc. | Fragrances and flavorants |
US6051258A (en) | 1995-06-07 | 2000-04-18 | Emisphere Technologies, Inc. | Proteinoid emulsions and methods for preparation and use thereof |
US5667806A (en) | 1995-06-07 | 1997-09-16 | Emisphere Technologies, Inc. | Spray drying method and apparatus |
US5750147A (en) | 1995-06-07 | 1998-05-12 | Emisphere Technologies, Inc. | Method of solubilizing and encapsulating itraconazole |
US6100285A (en) | 1995-06-07 | 2000-08-08 | Emisphere Technologies, Inc. | Method of solubilizing itraconazole |
US6461545B1 (en) | 1995-06-07 | 2002-10-08 | Emisphere Technologies, Inc. | Method of solubilizing and encapsulating itraconazole |
US6084112A (en) | 1995-09-11 | 2000-07-04 | Emisphere Technologies, Inc. | Method for preparing ω-aminoalkanoic acid derivatives from cycloalkanones |
US6375983B1 (en) | 1996-06-14 | 2002-04-23 | Emisphere Technologies, Inc. | Microencapsulated fragrances and method for preparation |
US5804688A (en) | 1997-02-07 | 1998-09-08 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US6242495B1 (en) | 1997-02-07 | 2001-06-05 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US6313088B1 (en) | 1997-02-07 | 2001-11-06 | Emisphere Technologies, Inc. | 8-[(2-hydroxy-4-methoxy benzoyl) amino]-octanoic acid compositions for delivering active agents |
US6060513A (en) | 1997-02-07 | 2000-05-09 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5990166A (en) | 1997-02-07 | 1999-11-23 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5939381A (en) | 1997-02-07 | 1999-08-17 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5879681A (en) | 1997-02-07 | 1999-03-09 | Emisphere Technolgies Inc. | Compounds and compositions for delivering active agents |
US5876710A (en) | 1997-02-07 | 1999-03-02 | Emisphere Technologies Inc. | Compounds and compositions for delivering active agents |
US5863944A (en) | 1997-04-30 | 1999-01-26 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5962710A (en) | 1997-05-09 | 1999-10-05 | Emisphere Technologies, Inc. | Method of preparing salicyloylamino acids |
US8241670B2 (en) | 2004-04-15 | 2012-08-14 | Chiasma Inc. | Compositions capable of facilitating penetration across a biological barrier |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0366277B1 (fr) | Formulations pharmaceutiques | |
US6951655B2 (en) | Pro-micelle pharmaceutical compositions | |
AU656134B2 (en) | Pharmaceutical formulations | |
US5206219A (en) | Oral compositions of proteinaceous medicaments | |
KR900001074B1 (ko) | 약제학적 조성물 | |
KR100638041B1 (ko) | 수용성 약물의 경구투여용 나노입자 조성물 및 그의제조방법 | |
EP0494654A2 (fr) | Composition pharmaceutique stable et procédé de production | |
JP4880461B2 (ja) | 治療薬用のマイクロ粒子脂肪酸塩固体製剤 | |
WO2008132731A2 (fr) | Procédés et compositions pour administration rectale d'insuline |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
AK | Designated contracting states |
Kind code of ref document: A2 Designated state(s): AT BE CH DE ES FR GB GR IT LI LU NL SE |
|
PUAL | Search report despatched |
Free format text: ORIGINAL CODE: 0009013 |
|
AK | Designated contracting states |
Kind code of ref document: A3 Designated state(s): AT BE CH DE ES FR GB GR IT LI LU NL SE |
|
17P | Request for examination filed |
Effective date: 19910520 |
|
17Q | First examination report despatched |
Effective date: 19920525 |
|
GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
ITF | It: translation for a ep patent filed |
Owner name: BARZANO' E ZANARDO ROMA S.P.A. |
|
AK | Designated contracting states |
Kind code of ref document: B1 Designated state(s): AT BE CH DE ES FR GB GR IT LI LU NL SE |
|
REF | Corresponds to: |
Ref document number: 98480 Country of ref document: AT Date of ref document: 19940115 Kind code of ref document: T |
|
REF | Corresponds to: |
Ref document number: 68911473 Country of ref document: DE Date of ref document: 19940127 |
|
ET | Fr: translation filed | ||
REG | Reference to a national code |
Ref country code: GR Ref legal event code: FG4A Free format text: 3010799 |
|
PLBE | No opposition filed within time limit |
Free format text: ORIGINAL CODE: 0009261 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT |
|
REG | Reference to a national code |
Ref country code: ES Ref legal event code: FG2A Ref document number: 2060785 Country of ref document: ES Kind code of ref document: T3 |
|
26N | No opposition filed | ||
EAL | Se: european patent in force in sweden |
Ref document number: 89309989.5 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: SE Payment date: 20000906 Year of fee payment: 12 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: FR Payment date: 20000912 Year of fee payment: 12 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: AT Payment date: 20000913 Year of fee payment: 12 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: LU Payment date: 20000925 Year of fee payment: 12 Ref country code: ES Payment date: 20000925 Year of fee payment: 12 Ref country code: DE Payment date: 20000925 Year of fee payment: 12 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: GB Payment date: 20000927 Year of fee payment: 12 Ref country code: CH Payment date: 20000927 Year of fee payment: 12 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: NL Payment date: 20000928 Year of fee payment: 12 Ref country code: GR Payment date: 20000928 Year of fee payment: 12 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: BE Payment date: 20001117 Year of fee payment: 12 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LU Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20010929 Ref country code: GB Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20010929 Ref country code: AT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20010929 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: SE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20010930 Ref country code: LI Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20010930 Ref country code: GR Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20010930 Ref country code: ES Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20010930 Ref country code: CH Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20010930 Ref country code: BE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20010930 |
|
REG | Reference to a national code |
Ref country code: GB Ref legal event code: IF02 |
|
BERE | Be: lapsed |
Owner name: PATRALAN LTD Effective date: 20010930 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: NL Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20020401 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: DE Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20020501 |
|
EUG | Se: european patent has lapsed |
Ref document number: 89309989.5 |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: PL |
|
GBPC | Gb: european patent ceased through non-payment of renewal fee |
Effective date: 20010929 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: FR Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20020531 |
|
NLV4 | Nl: lapsed or anulled due to non-payment of the annual fee |
Effective date: 20020401 |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: ST |
|
NLV4 | Nl: lapsed or anulled due to non-payment of the annual fee |
Effective date: 20020401 |
|
REG | Reference to a national code |
Ref country code: ES Ref legal event code: FD2A Effective date: 20021011 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: IT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES;WARNING: LAPSES OF ITALIAN PATENTS WITH EFFECTIVE DATE BEFORE 2007 MAY HAVE OCCURRED AT ANY TIME BEFORE 2007. THE CORRECT EFFECTIVE DATE MAY BE DIFFERENT FROM THE ONE RECORDED. Effective date: 20050929 |